新規α1グロビンバリアント（HBA1:c.-35T>C）と中国集団で初めて報告されたHb M-Saskatoonの複合体

Hemoglobinopathies are genetic disorders characterized by structural or quantitative hemoglobin abnormalities. We report the first documented case globally of a novel alpha1 (α1)-variant (HBA1:c.-35T>C) co-occurring with Hb M-Saskatoon (HBB:c.190C>T), the latter being identified for the first time in the Chinese population.

Peripheral blood samples were obtained from a 3-year-old Chinese girl presenting with persistent cyanosis, including complete blood count, hemoglobin electrophoresis, and degenerative globin body testing. Hemoglobin variants detected were subsequently characterized through DNA sequencing.

The research subject was diagnosed with different types of abnormal Hb. Hematological analysis revealed normocytic normochromic erythrocytes with mild anemia (Hb 111 g/L, reference 112-149 g/L). Electrophoretic analysis detected abnormal hemoglobin fractions: abnormal Hb bands in zone I and s in the E zone near the position of Hb A₂. Targeted sequencing demonstrated compound heterozygosity for α1-variant (HBA1:c.-35T>C) with Hb M-Saskatoon (HBB:c.190C>T).

We confirmed Hb M-Saskatoon (HBB:c.190C>T) co-occurring with a globally unreported α1-variant (HBA1:c.-35T>C) in a Chinese proband. This dual variant expands the global hemoglobinopathy registry and provides critical insights for diagnosing atypical cases, particularly in populations with understudied genetic diversity. This finding elucidates novel genotype-phenotype correlations in complex hemoglobinopathies and underscores the imperative of genetic testing for atypical presentations.